Scientists are investigating how to treat pain in babies who can’t tell you when it hurts.
When Mats Eriksson was just starting off as a nurse in the neonatal intensive care unit in the 1980s, he truly hated one part of his job. To draw blood for the daily metabolic test, he had to prick the babies’ heels with a tiny lancet and squeeze their heels to collect enough blood for analysis. It was hard to do, and hard to watch.
“The children were crying, the mothers almost fainted,” he says. “I was sweaty all over. It was a really tough job for everyone. And we had nothing to offer.”
By anything to offer, he means drugs to treat the infants’ apparent pain. Strong drugs like morphine can be dangerous for such young bodies. Even everyday drugs like Tylenol and Advil can be harmful to use in infants because of their potential impacts on the liver and kidneys.
But a bigger reason why was more frustrating. “In those days, we did not believe that they could feel pain,” he says of infants. “We could see it, of course, but science said ‘no.’”
The NICU (neonatal intensive care unit) is where infants who are born prematurely — meaning infants born before 37 weeks of pregnancy — and full-term infants (who are born around 39 or 40 weeks) with health issues spend the first weeks and, often, months of their lives. Every day, they encounter painful pricks and prods from hospital staff to monitor them and keep their frail bodies alive. Eriksson recalls that even when the children needed invasive procedures like open-heart surgeries, they were done without any anesthesia or pain medication.
Since then, a lot of progress has been made in recognizing that premature babies in the NICU can feel pain — and, more importantly, that the pain matters.
Even though the infants will not remember the distress, it’s believed these painful experiences add up to something like a lasting psychological injury, impacting brain development and their ability to regulate emotions later in life.
But how to treat this pain — and even how to recognize it in the moment, as some preterm babies are too weak to cry? Those are still questions without perfect answers.
“We’ve been poor, and continue to be poor, at recognizing pain and distress in our babies,” says Terrie Inder, the chair of pediatric newborn medicine at Brigham and Women’s Hospital in Boston. “And we don’t know how to treat it. That’s all absolutely true.”
But now scientists like Inder are asking: Could one solution be as simple as skin-to-skin contact — loving touch — from a parent? The experience of pain in the NICU seems to shadow children as they grow up, leaving them at increased risk for developmental challenges and behavioral struggles. If there really is a healing power in touch, “that could make a lifetime of difference,” Inder says.
From almost universal loss to survival
There’s a lot about treating some of the most vulnerable, tiniest humans on Earth that’s sad and frustrating. But let’s start with the good news: The NICU is a true modern miracle, a place where many waking nightmares turn into stories with happy endings.
Naomi Rendina experienced this for herself. Today, she’s a PhD medical historian. But 13 years ago, she was 22 years old and pregnant for the first time.
“I spent my whole life imagining what it was going to be like to be pregnant and what it was going to be like to be a mom,” Rendina says. When she got pregnant, she was so excited.
But when she was 30 weeks pregnant, she went in for a checkup. “It went very quickly from a very healthy, very normal pregnancy to a very dangerous, very scary pregnancy,” she says.
Her blood pressure was high. That was just the start. She had preeclampsia, a dangerous condition that can in some cases be deadly. Her liver was creating enzymes that her kidney could not filter out. “And because of the proteins in the blood,” she says, “my heart was working exceptionally hard. My body couldn’t handle it.”
Rendina’s life was at risk, and the only solution was to deliver her baby more than two months early. She was scared.
Rendina was taken to a nearby hospital, where she had an emergency C-section. There, the medical staff brought her daughter out backward, or, as Rendina puts it, “butt to the world.”
Rendina waited to hear a cry.
It was silent for what felt like the longest time.
But then, there it was. “But it wasn’t the scream of a newborn,” she says. “It sounded like the tiniest little kitten. It was so tiny, but it was there. She made that effort and she cried.”
The tiny voice was coming from a teensy 2-pound, 7-ounce body that needed help breathing for the first few hours of her life. “She looked like a baby, but without all the chonk,” Rendina says. She needed to grow.
That was the beginning of a 92-day hospital stay in the NICU until her daughter was strong and developed enough to go home. While the baby didn’t need any large invasive surgeries, it wasn’t an easy experience. Every day, there were these pricks and prods like those Eriksson described to draw drawn from the baby’s heel. There were lots of intravenous needles placed into her veins, and sometimes the veins ruptured.
Even in the 2000s, Rendina recalls that the medical staff told her the baby wasn’t feeling pain. Instead, they used terms like “sensory overload,” she says.
Every NICU infant’s experience is different. But Rendina suspects her daughter suffered some psychological and behavioral consequences as well. She was late to learn to walk, and had night terrors as an infant. Rendina can’t be sure they were the result of the NICU stay, but she wonders if it was because her daughter was having dreams of being confined.
Rendina’s daughter is now healthy, and recently celebrated her 13th birthday. “She is a delightful young woman,” Rendina says, kvelling. “She is smart. She’s adventurous. She’s beautiful. I’m only a little biased.”
These days, a lot of stories like Rendina’s end well. Children born around 28 weeks — that’s 12 weeks early — have an 80 to 90 percent chance of surviving. They grow up to be healthy kids, albeit sometimes with some extra health or developmental challenges. But just a few generations ago, the technology didn’t exist to save them. In the 1960s, more than half of all infants born in the US before 32 weeks died.
“The progress in neonatal medicine has been startling,” Inder says, going from “almost universal loss to almost universal survival.” That is, at least in wealthy countries like the United States; there are still large global disparities in preterm infant survival.
That swing from loss to survival started in the ’60s, catalyzed by the death of Patrick Kennedy — the infant son of President John F. Kennedy and first lady Jacqueline — who was born five-and-a-half weeks premature and died of respiratory distress syndrome. In the wake of the first family’s tragedy, money and attention poured into NICU research.
With the money and attention came progress. In the next decades, doctors were able to miniaturize medical equipment for use on preterm infants. Critically, they discovered premature lungs needed a substance called surfactant that aids in breathing. Now, “a baby can be born four months early and we are able to provide lifesaving treatments,” Inder says.
It’s miraculous progress. But amid all this advancement, medical researchers overlooked pain. They didn’t think these preterm infants — or any infants — could feel it.
How doctors learned premature infants felt pain
Pain is complicated, even in adults. In premature infants, it’s even harder to pinpoint.
Throughout our bodies, there are receptors that sense mechanical forces, like touch and pain. These are the doorways through which forces from the outside world enter our nervous systems. There’s one for light touch, like the graze of a finger against your arm; then there are even different doorways for heat and cold.
But ultimately, pain is something we experience in our brains. “So the central dilemma is how to recognize pain in these babies, because they can’t talk and tell us what they’re experiencing,” Inder says.
And so, for a long while, doctors knew that these preterm infants had the nerves to sense pain, but they didn’t think the brain had developed enough to experience it.
“They see it almost like a blob of clay that hasn’t got the same degree of integrity, experience, and capacity to feel and experience,” Inder says. “This was very much the case for the premature baby, who was believed in these early years, right through into the ’80s, to not experience pain because they weren’t fully developed. So surgical procedures — such as open-heart surgery — were done without any anesthesia or pain relief during this period.”
“The turning point,” Inder says, “came from the observations of a pediatric anesthesiologist who noted that during these open-chest cardiac procedures that were done on these babies without any anesthesia or pain relief, the heart rate went up dramatically.” That indicated there was some sort of pain response happening with the infants.
“So he began also measuring other markers of stress hormones and showed that indeed there were these dramatic rises in stress hormones, indicating the baby indeed was experiencing distress at the time of this surgical procedure,” she says. “This was in the late ’70s, early ’80s. And I hate to say that the evolution of knowledge and understanding is still in progress.”
Babies don’t remember the pain, but there’s evidence it could still leave a scar
Today, doctors and medical researchers acknowledge these young infants can feel pain. And in some ways, the pain they feel might be worse than what adults feel.
“They can’t localize the pain the same way that we can as adults,” Inder says. “So a heel prick on the back of the heel can feel as though it’s coming somewhere from the whole foot or even the leg. So it’s a much more diffuse and impactful kind of pain.”
But what Inder and her colleagues say is the problem with pain in the NICU is that it’s not just about any one moment of it. NICU stays can last months. And every day, the babies encounter many painful things.
“The average premature baby will go through at least 10 to 12 unpleasant or painful experiences every 24 hours for the first four weeks of life,” Inder explains. That can include surgery, but also less dramatic procedures like placing feeding or breathing tubes through the nose or mouth, or drawing blood.
These moments of pain matter not just because they’re feeling pain in those moments. Rather, it seems that a large volume of pain, over time, is suspected to cause or contribute to negative changes in brain development.
The number of painful experiences a premature infant has — regardless of how sick they are — is correlated with negative changes in brain development. The more pain, the worse the outcomes.
“What we see is smaller hippocampus, the memory area, smaller amygdala, which is the area for emotional processing,” Inder says. “We see alterations in the cerebellum, which is a critical area for language and motor development. These are all very important regions for later childhood and adult brain.“
Those changes manifest in lower IQ, lower language skills, poorer attention, and poorer emotional regulation. There’s even evidence to suggest that this exposure to pain leaves them with a lower pain threshold later in life, too.
How, exactly, pain causes these changes is still a topic of ongoing research. But Inder says it has to do with the fact that in the last 12 weeks of a pregnancy — the weeks in the womb that are missed due to a premature birth — a lot of brain development is still happening.
During that time, “your brain goes from being completely smooth to being completely folded, just like the adult brain,” she says. “And so this period is very sensitive to any environmental influences.”
The problem is that the still-developing brain is also sensitive to pain-killing drugs like opiates. “The opiate medications are sort of like bringing out an AK-47 to take down the problem,” Inder says. For one, she says opiates are better at treating the intense, acute pain of a surgical operation, and are less effective for the repeated, chronic type of pain the infants more regularly experience. “It doesn’t improve brain development to give opiates,” Inder says. “And if anything, there may be additional negative effects on development,” she says.
Instead of opiates, “we may need something gentler and kinder,” she says.
The hope is that if researchers can find ways to treat pain in these premature babies, then perhaps they can stave off the changes in brain development. And, thankfully, the ideas to do it are very simple. But they would take a lot of societal investments to implement.
The healing power of touch
Eriksson, the NICU nurse who got sweaty taking blood samples from babies, turned his discomfort with infants’ pain into inspiration for research. Today, he runs an international research group based in Sweden called Pain in Early Life, or PEARL. He and his colleagues study simple ways to alleviate infants’ pain without drugs.
For instance: He’ll use sugar. “Glucose, as a pain relief,” he says. Yes, a spoonful of sugar can help the medicine go down. If he feeds an infant some sugar before drawing blood from their heel, “they don’t react anymore,” he says. “The work has been to try to explain why this works and nobody actually has.”
Regardless of how it works, sugar isn’t an ideal solution either. Too much sugar in the NICU is also associated with negative effects on cognitive development. (Yes, treating premature infant pain is hard!)
So while there is a place for glucose in treating pain, Eriksson and his colleagues prefer an even simpler and potentially more powerful idea: parent’s touch, or skin-to-skin contact — placing preterm babies directly on a parent before doing something painful. Any skin contact seems to help, but research suggests that parents’ touch is more effective than that of a stranger’s (slightly favoring mothers over fathers).
“When you draw blood from an infant who is lying on their mother or father, and you don’t see any reaction on the infant … that doesn’t happen all the time, but when it happens, it feels very good,” says Emma Olsson, a NICU nurse and researcher in Sweden who works with Eriksson.
This approach is sometimes called “kangaroo care.” And it’s not super rare; it’s common practice in the US for infants to be placed directly on a parent’s bare chest immediately after birth. It’s also used in US NICUs. What’s different is that the course of treatment the Swedish researchers advocate for is much, much more involved than what typically occurs.
In Sweden, parents of children in the NICU are paid to stay in the hospital; they’re essentially recruited to be nurses to be around as much as possible for pain management. (Parents responsible for other children will often do shifts with a partner, Olsson explains.)
“In my 20 years at the NICU, I’ve gone from being the one taking care of the infant to guiding the parents, and then teaching them how to take care of their own infant,” Olsson says. “And that’s how it should be.” In Sweden, parents will hold their children through small procedures like blood draws, but also sometimes through more invasive ones like intubations (i.e. inserting a breathing tube). “Some might think that that’s not a good idea because it’s scary for the parents,” Olsson says. But if the parents are up to the task, she says, they’ll be put to use.
You might be thinking: Of course this works in Sweden, they have a large social safety net. But in the US?
NICU stays can last months, and many parents in the US just can’t always stay there the whole time. They may not be able to get medical or parental leave from work.
Rendina, the mother of the girl born at 30 weeks, had the resources to be with her child all the time. She felt really lucky. “Our hearts were crushed every day,” she says, “seeing the babies that weren’t being held because their parents were so busy working.”
“How can we expect them to take time off of work, to be able to get to the hospital or afford all of the [travel] every day to go see the baby,” says Rendina, who completed her dissertation on the history of the NICU, inspired by her own experience. “So we need to be creating these systems of support.”
How do we know if it’s working?
There’s a final wrinkle to the NICU-pain puzzle: It can be really hard to know if sugar or parental touch is working — or when to deploy them — because scientists don’t have objective tools to measure infants’ pain.
Right now, doctors and nurses mostly have to rely on subjective measures: by looking at the expression on their little baby faces or how they move their bodies.
But there are challenges here. “Babies cry and make these behaviors for many, many different reasons,” says Rebeccah Slater, a pediatric neuroscientist at the University of Oxford. “It might not be just whether they’re in pain.” There’s also the case that some preterm infants don’t cry out when something painful happens to them — because they are too weak.
So Slater wants to do better.
“My particular interest is trying to look at the brain,” Slater says, “to see what’s happening in the brain when babies experience pain, because fundamentally pain is an experience that happens in that organ.”
In her studies, Slater hooks a baby’s head up to an electroencephalogram (EEG), a device that measures electrical signals coming from the brain. “And so what we’ve been able to do is start looking at specific changes in brain activity when we know a procedure is happening that’s painful,” she says. “And in real time, we can look at these changes and get a score.” A pain score, that is.
Her big hope is that these pain scores can be used bedside to help nurses and doctors treat individual babies, though the technology isn’t ready to be deployed more broadly yet. “It’s all experimental,” she says.
Beyond the bedside, she wants these measures to be used in clinical trials. It’s hard to judge what treatments work more broadly without an objective measurement. That work is still underway. “We’re partway through a clinical trial, which is specifically looking at whether the parents who stroke their babies before a painful procedure can reduce the brain records I’ve been describing.”
Though how it works isn’t precisely known. The answer could be quite simple.
“I think we all feel better with the human touch,” Olsson says. “Skin-to-skin makes you feel very close to someone, either if it’s holding hands or just being near someone. I think that’s just how we are programmed.”
There are so many nerve endings on the skin, so many doorways to introduce a pleasant feeling into your body, to distract from, or even override, the pain.
“Think of yourself,” Eriksson says. “If you have a toothache, if someone holds your hand or gives you a hug, that relieves. Gentle human touch can be very good.”
For a premature infant, this touch is as close as they can get to being back in the womb. “You’re feeling your mother or father breathing,” Eriksson says. “You are snuggled up.”
In the place of proof, there’s hope
Let’s say all the ideal conditions are in place. Scientists build well-calibrated machines to objectively monitor an infant’s pain, and those monitors show that skin-to-skin contact is healing. And not only does it work, but society helps it happen: Parents are supported to stay in the NICU however long it takes and provide that healing touch. There are other ideas in the works too: redesigning NICU wards to be more soothing spaces, with calm music, better lighting, and more comfortable cribs.
Let’s say all that is implemented, a question remains: Would it work? Would it prevent some of the negative consequences of all those painful experiences, the altered brain development, the behavioral issues down the road?
It’s not currently known. “If we treat the pain here and now, I would hope that means that we will treat some of the negative consequences of the pain later in life,” Olsson says. “But I don’t have any scientific proof.”
It’s not possible to do a randomized controlled trial where some children get access to their parents’ touch and some don’t. “But if we change the system, if we are better, then we’ll hopefully see a better outcome,” Eriksson says. In the place of proof, there’s hope: “You need to have hope,” he says. “Otherwise I would not do this.”
When I asked Inder what she hoped people would take away from this story, she said she hoped that people just don’t feel despondent that babies are suffering. She wants them to know how resilient they can be, and how much joy they can bring, despite arriving with a rough start.
“Many babies are surviving through challenging times by their strong spirit and their strong will,” Inder says. “And we have enormous advances and technologies to help them. We just still have a gap in science to be able to do this really well.”
Rendina’s daughter still has some scars from NICU needles that were embedded in her hand. But to Rendina, these scars aren’t about pain; they’re about resilience.
“I showed her, last week, the scars on her hand,” Rendina says. “And reminded her that anytime that she has any sort of doubt about herself, or doubts of her capability, to look at her hand. Those little scars are there to remind her that she’s capable of more than she’ll ever even understand. Because those are her scars of her time in the NICU — and her reminder that she’s my hero.”